Despite enormous investments of financial and human resources, cancer remains one of the major causes of death. Current cancer therapies cure only about fifty percent of the patients who develop a malignant tumor. In most human malignancies, metastasis is the major cause of death.
Metastasis is the formation of a secondary tumor colony at a distant site. It is a multistep process of which tumor invasion is an early event. Tumor cells locally invade host tissue barriers, such as the epithelial basement membrane, to reach the interstitial stroma, where they gain access to blood vessels (“hematogenous metastasis”) or lymphatic channels for further dissemination. After invading the endothelial layer of a vessel wall, the circulating tumor cells are dislodged into the circulation and arrested in the precapillary venules of the target organ by adherence to endothelial cell lumenal surfaces, or exposed basement membranes. The tumor cells again invade the vascular wall to enter the organ parenchyma. Finally, the extravasated tumor cell grows in a tissue different from where it originated.
As cancer treatments using radiation and/or chemotherapies become more effective, and more people live for longer periods of time following treatment, cancer survivors are faced with a significant risk of developing therapy-induced secondary tumors.
Because of the inherent mutagenicity of ionizing radiation and most anti-cancer drugs, investigators predicted that therapy-induced secondary tumors would become a major health issue.
Due to the difficulties in the current approaches to the treatment and prevention of metastases, there is a need in the art for novel therapeutically useful compounds for preventing individuals from the occurrence of metastasis in the course of a cancer.
Additionally, In most human malignancies, distant metastases are often too small to be detected at the time the primary tumor is treated. Furthermore, widespread initiation of metastatic colonies usually occurs before clinical symptoms of metastatic disease are evident. The size and age variation in metastases, their dispersed anatomical location, and their heterogeneous composition are all factors that hinder surgical removal and limit the concentration of anticancer drugs that can be delivered to the metastatic colonies.
Accordingly, there is still a need in the art for methods that will allow the one skilled in the art to determine the status of progression of cancers in patients so as to enable a precise prognosis of the evolution of the disease, including the occurrence of metastasis, and also to enable a precise monitoring of the therapeutical treatment which may be the more beneficial to the patient, once taken into account the progression status of the cancer. For example, there is a need in the art for novel biological markers which are indicative of the occurrence of a cancer. These novel biological markers might be used in combination with one or several already known markers.
The present invention fulfils these needs and further provides other related advantages.